ATH434 Phase 2 Trial Shows Significant Efficacy for MSA Patients

In a promising development for patients suffering from multiple system atrophy (MSA), investigational drug ATH434 has demonstrated significant therapeutic efficacy according to the latest data from an open-label Phase 2 trial. The trial, known as ATH434-202, involved 10 patients who received 75 mg of ATH434 twice daily over a 12-month period. Results indicated noteworthy improvements in neurological symptoms and biomarkers, offering hope for a disease-modifying treatment in a condition currently lacking effective medications.

The trial findings were announced on July 28, 2025, by Alterity Therapeutics, who are spearheading the development of ATH434. Principal investigator Dr. Daniel Claassen, a Professor of Neurology at Vanderbilt University Medical Center, emphasized the significance of these results, noting, "These results are very helpful in establishing the clinical response to therapy. The consistent changes in UMSARS, along with quantitative measures in imaging, support the findings we noted in Study 201.”

MSA is a rare neurodegenerative disorder characterized by the accumulation of abnormal proteins, leading to progressive motor dysfunction. The open-label study recorded mean increases in the Modified Unified MSA Rating Scale Part I (UMSARS I) scores, with 43% of patients demonstrating stable scores at the conclusion of the study. Importantly, the treatment was associated with a reduction in brain iron accumulation, a key biomarker linked to disease progression.

Dr. Claassen's research indicates that ATH434's mechanism of action involves inhibiting the aggregation of pathological proteins associated with neurodegeneration. Over the 12-month period, patients showed a mean z-score of –0.44 on the MSA Atrophy Index (MSA-AI), consistent with observations from a previous trial. Furthermore, the safety profile of ATH434 appears favorable, as no serious adverse events were reported, and any mild to moderate adverse events were consistent with previous studies.

Dr. David Stamler, CEO of Alterity Therapeutics, expressed optimism regarding the implications of these findings, stating, "I am very encouraged by the positive results from the ATH434-202 trial, as they reinforce the robust efficacy we observed in our double-blind study. We continue to believe that ATH434 has the potential to slow the progression of this devastating disease."

The trial's results also highlighted that 30% of participants exhibited stabilization or improvement in overall neurological symptoms, as evaluated by both clinician-rated and patient-reported scales. Symptoms of orthostatic hypotension, a common complication of MSA, remained stable among participants throughout the study.

ATH434's potential as a disease-modifying therapy is underscored by its ability to reduce iron accumulation in critical brain regions such as the globus pallidus and putamen. The implications of these findings extend beyond MSA, as they may pave the way for future treatment options for other neurodegenerative disorders characterized by similar pathological mechanisms.

Looking ahead, the results from the ATH434-202 trial encourage further development and investigation into ATH434's efficacy and safety in larger populations, as currently, there are no approved disease-modifying therapies for MSA. As the research progresses, stakeholders remain hopeful that advancements in treatment could significantly enhance the quality of life for patients affected by this challenging condition.